Harnessing bacteriocin biology as targeted therapy in the GI tract

Abstract

ABSTRACTRecently, our laboratory demonstrated that bacteriocins produced by commensal enterococci provide an advantage in niche maintenance in the highly competitive environment of the gastrointestinal (GI) tract. Bacterial production of bacteriocins is a conserved defense strategy to help establish an ecological niche. Bacteriocin-encoding genes in enterococci are often carried on mobile genetic elements, including conjugative plasmids, enabling the transfer of such traits to other community members in a shared niche. Use of a novel mouse model for enterococcal colonization of the GI tract allowed us to investigate enterococcal dynamics and the role of enterococcal bacteriocins in the mouse GI tract. We examined the role of bacteriocin-21, carried on the pPD1 plasmid, in enterococcal colonization of the gut. We discovered that Enterococcus faecalis (EF) harboring pPD1 effectively colonizes the GI tract by using Bac-21 to eliminate its competition. In our study, we also present evidence for active conjugation in the GI tract, a strategy EF uses to enhance the number of bacteriocin producers in a given niche and eliminate bacteriocin-susceptible populations. Using an engineered strain of EF that is capable of producing Bac-21 but impaired in its conjugation ability, we were able to reduce pre-existing colonization by vancomycin-resistant enterococci in the mouse gut. Thus, our results suggest a novel therapeutic strategy to de-colonize antibiotic-resistant enterococci from the GI tract of patients and thereby prevent the emergence of resistant enterococcal infections that are otherwise difficult, or impossible, to treat.